Department of Neuroscience and Biomedical Technologies, University of Milano-Bicocca, San Gerardo Hospital, Monza, MI, Italy.
Published: October 2004
AI Article Synopsis
Article Abstract
Leber hereditary optic neuropathy (LHON) is a maternally inherited form of retinal ganglion cell degeneration leading to optic atrophy which is caused by point mutations in the mitochondrial genome (mtDNA). Three pathogenic mutations (positions 11778/ND4, 3460/ND1 and 14484/ND6) account for the majority of LHON cases and they affect genes that encode for different subunits of mitochondrial complex I. Excitotoxic injury to retinal ganglion cells and the optic nerve has been previously hypothesized, especially given the high susceptibility of this neural cell type to glutamate toxicity. Osteosarcoma-derived cytoplasmic hybrids (cybrids) generated from six unrelated LHON patients, two cell lines for each pathogenic mutation, were compared with cybrids obtained from three healthy controls. Molecular and biochemical analyses showed that excitatory amino acid transporter 1 (EAAT1)/GLAST is the most active glutamate transporter in this cellular model. The glutamate uptake maximal velocity was significantly reduced in all LHON cybrids compared with control cybrids. This reduction was correlated in a mutation-specific fashion with the degree of mitochondrial production of reactive oxygen species, which is enhanced in LHON cybrids. Our findings support the hypothesis that the genetically determined mitochondrial dysfunction in LHON patients leads to impaired activity of the EAAT1 glutamate transporter. This observation is particularly relevant since EAAT1 is the major means of glutamate removal in the inner retina and this prevents retinal ganglion cells being damaged as a result of excitotoxicity.
Background: Retinal ganglion cell (RGC) death caused by acute ocular hypertension is an important characteristic of acute glaucoma. Receptor-interacting protein kinase 3 (RIPK3) that mediates necroptosis is a potential therapeutic target for RGC death. However, the current understanding of the targeting agents and mechanisms of RIPK3 in the treatment of glaucoma remains limited.
Background: Bipolar disorder (BD) is a psychiatric condition with significant health implications due to its comorbidities, premature mortality, and functional impairments. Despite extensive research on treatment and rehabilitation, gaps remain in diagnosis and monitoring. Therefore, there is a need for biomarkers to identify individuals at risk for disease progression or excacerbation.
Barcelona Clinic Schizophrenia Unit, Institute of Neurosciences, Hospital Clinic, Barcelona, Spain; Institut d'Investigacions Mèdiques August Pi i Sunyer (IDIBAPS), Fundació Clínic, Barcelona, Spain; Biomedical Research Networking Centre Consortium on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain. Electronic address:
Emerging evidence suggests that retinal structural alterations are present in schizophrenia spectrum disorders (SSD), potentially reflecting broader neurodevelopmental and neurodegenerative processes. This cross-sectional study investigates retinal thickness and its clinical correlations in a sample of early-course SSD patients compared to healthy controls (HCs). One hundred-two eyes from 26 SSD cases and 25 age- and sex-matched HCs were included.
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Laboratory of Veterinary Biochemistry, College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University, Jeju, 63243, South Korea.
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